"Organ Failure in Sepsis: Understanding the Role and Impact of Bilirubin on Liver"

Overview:

Sepsis is a life-threatening condition that happens when the body’s immune system has an extreme response to an infection, causing organ dysfunction. The body’s reaction causes damage to its own tissues and organs and it can lead to shock, multiple organ failure and sometimes death, especially if not recognized early and treated promptly.

Sepsis can affect anyone, but people who are older, very young, pregnant or have other health problems are at higher risk.

Common signs of sepsis include fever, fast heart rate, rapid breathing, confusion and body pain. It can lead to septic shock, multiple organ failure and death.

Sepsis is usually caused by bacterial infections but may be the result of other infections such as viruses, parasites or fungi. Its treatment requires medical care, including the use of antimicrobials, intravenous fluids and other measures.

The immune response induces a severe macro and microcirculatory dysfunction that leads to a profound global hypoperfusion, injuring multiple organs. Consequently, patients with sepsis might present dysfunction of virtually any system, regardless of the site of infection. The organs more frequently affected are kidneys, liver, lungs, heart, central nervous system, and hematologic system.

There are tools to assess the severity of the disease that can also help to guide treatment, like the Sequential Organ Failure Assessment (SOFA) score. You can check another blog related to SOFA score where I explained in detail here is the link(https://www.numpyninja.com/post/sequential-organ-failure-assessment-sofa-score-your-body-s-red-flag-for-organ-distress ). In this blog we are focusing on how bilirubin play a major role in liver dysfunction.

Serum bilirubin is the most widely used biomarker to diagnose hepatic dysfunction during sepsis. In a large Austrian multicentric cohort, early increase in plasma bilirubin (>2 mg/dl), noted in approximately 10% of critically ill intensive care patients and many of whom were septic, was a strong independent risk factor for subsequent mortality. After multivariable adjustment for potential confounding factors, elevated serum bilirubin levels within 72 h of admission were associated with an increased risk of mortality in patients with severe sepsis and septic shock. However, bilirubin level lacks specificity to reflect the full spectrum of liver dysfunction and differentiate an acute response from a preexisting organ chronic disease.

Patients aged 61 years or older were prone to sepsis-associated liver injury, whereas it was rare in patients aged 15–60 years. Age-related host immunological potency, malignant neoplasms, diabetes mellitus, and cerebrovascular diseases might be potent risk factors in the elderly. Interestingly, development of jaundice in elderly patients with bacterial sepsis was associated with increased survival. This result may represent robust immunity in elderly patients with sepsis, which might be responsible for their survival.

 1. Bilirubin Total:

The total bilirubin level represents the sum of both indirect and direct bilirubin.

 Bilirubin is a yellowish pigment that is produced during the normal breakdown of red blood cells in the body. It is a byproduct of the heme component of hemoglobin, which is released when old or damaged red blood cells are broken down. Bilirubin is processed by the liver and excreted into the bile, ultimately leaving the body through feces. Bilirubin exists in two main forms: indirect (or unconjugated) bilirubin and direct (or conjugated) bilirubin.

Elevated bilirubin levels in sepsis can be indicative of liver dysfunction. The liver plays a crucial role in processing bilirubin, and when the liver is affected by the inflammatory response associated with sepsis, it may struggle to process bilirubin efficiently. This can result in an increase in both indirect (unconjugated) and direct (conjugated) bilirubin levels.

Normal range of Total bilirubin: 0.1 to 1.2 mg/dL (1.71 to 20.5 µmol/L)

2. Bilirubin Direct: (also called conjugated)

 Normal range of bilirubin direct: less than 0.3 mg/dL (less than 5.1 µmol/L)

Organ Failure:

In severe cases of sepsis, multiple organ failure can occur. The liver is particularly susceptible to damage during sepsis, and impaired liver function can contribute to elevated bilirubin levels.

(photo courtesy: https://media.geeksforgeeks.org/wp-content/uploads/20240326175833/Difference-between-Direct-and-Indirect-Bilirubin.webp)

Organs Affected

               - Liver Dysfunction, Brain, Kidneys, Gastrointestinal System

 Symptoms

                - Jaundice, Dark Urine, Pale Stool, Itching, Abdominal Pain, Nausea and Vomiting

What does bilirubin do in your body?

Bilirubin is a waste product of expired red blood cells. Normally, your body expels it through your intestines. On its way out, though, it may provide some benefits. Current studies suggest it may act as an antioxidant that helps protect against cardiovascular disease. However, too much can be toxic. If it builds up in your blood, it can make you feel ill. It can also irritate nerves under your skin, making it itch.

What causes high bilirubin levels (hyperbilirubinemia)?

Bilirubin might build up in your blood if:

Your body breaks down too many red blood cells too fast. You might be overproducing bilirubin if you have a blood disorder, such as hemolytic anemia, that destroys red blood cells.

Your liver is struggling to process its normal load of bilirubin. Your liver might struggle with occasional toxic overload, or it might have a chronic liver disease that affects its functioning.

Your biliary system isn’t clearing bile efficiently. There might be a blockage in your bile ducts or your gallbladder that’s causing bile to back up and leak into your bloodstream.

What are symptoms of high bilirubin?

High bilirubin leads to jaundice, a yellow cast to your skin and the whites of your eyes. Jaundice is often the first symptom that would prompt a healthcare provider to check your bilirubin levels. High bilirubin in your blood can also leak out in your pee, making it darker. If bilirubin isn’t coming out in your poop as it should, your poop might be lighter or clay-colored. Very high bilirubin can make you itch (pruritus).at causes high bilirubin levels (hyperbilirubinemia)? 

What causes low bilirubin levels (hypo bilirubinemia)? 

Certain medications can lower your bilirubin levels, including antibiotics, birth control pills, sleeping pills and seizure medications. Low levels aren’t generally a cause for concern. 

Lets take one analysis and understand about how bilirubin affects on liver in case of SEPSIS.

I choose one data set which include patient’s detail who has sepsis or sever sepsis stages and how their organ misfunctioning.

To analyze this data, I load it in to tableau service where I can create a different visuals to check within group of people who are affected with SEPSIS.

Graph 1. Range of Bilirubin Direct

lets take category of bilirubin range to understand how many patients comes under high or low range.

Create one calculation field where we can categorize bilirubin in 3 different category Normal, High(Jaundice) & severe bilirubin is Severe sepsis.

Use this calculation field to check how many patients have severe range of bilirubin

In this bubble chart we can clearly see that there are 2931 patients have sever sepsis problem and if we calculate SOFA score then they might face problem with liver damage.

Graph 2: Bilirubin level in Male & Female

 Let’s analyze in gender who is more prone to bilirubin

As per taken data total severe sepsis patients are 2,931 and as per analysis, I can clearly say that bilirubin is affected more in male compare to female as in gender analysis male are more than female in severe condition with bilirubin

Graph 3. Bilirubin range based on Age & Gender

Next let’s analyze bilirubin range within age group.

Here you can see I created 1 graph where clearly explained about no of Patient for each Age (bin of 10) broken down by Gender (Male & Female). Color shows details about Bilirubin Direct Range as yellow color represents Sever sepsis and orange color represents high level followed by normal. Size shows details about Bilirubin Direct Range. I used same calculated field for Bilirubin Range.

the higher range of bilirubin direct is more in Male at the age of 60 and in females at the age of 70. As compared to gender male are more than female and in no. of patients count (425) are also more in male age 70 and in female (300).

Overall, we can say that liver failure disease is a problem more in male at the age of 70 than females.

 Here is dashboard where I have created more analysis about patient’s condition and how long they stay at hospital or in ICU. Check all analysis in detail.

In liver dysfunction, doctors look at more than just bilirubin levels. They focus on:

1.   Liver Enzymes (ALT and AST): Both Enzymes indicate that might have problem in Liver cells.

2.  Alkaline Phosphatase (ALP): High levels of ALP in body means bile production is not proper.

3.  Albumin: Low levels of albumin cause production of protein in liver.

4.  Prothrombin Time (PT): how long it takes blood to clot, longer clotting time can signal liver problems.

5.  Platelet: Low platelet counts in liver cause liver disease

6.  WBC(White Blood Cells): Low or High level of WBC can indicate inflammation or infection

 These tests provide a clear picture of how well your liver is functioning.

Treatment:

In patients who develop hyperbilirubinemia with normal aspartate transaminase and alanine transaminase in the setting of infectious symptoms, minimum workup includes urine analysis, blood test, urine test, and chest x-ray to identify a source of infection.

If an infectious cannot be readily identified, further testing should be performed to determine the causes. There are no specific guidelines for the management of liver dysfunction in sepsis; however, early goal-directed fluid resuscitation, early initiation of antibiotics to control the source of infection, and vasopressor support for optimal organ perfusion may minimize or prevent liver Damage.